1. Field of the Invention
This invention relates to active peptide fragments of vasoactive peptides, their method of preparation, and areas of use.
2. Description of the Prior Art
The vasoactive intestinal peptide (VIP) was discovered and isolated in pure form from porcine intestines as disclosed in U.S. Pat. No. 4,119,118 of Said and Mutt. This vasoactive intestinal peptide was synthesized as reported in U.S. Pat. No. 3,862,927. A related peptide isolated from chicken or other fowl is reported in U.S. Pat. No. 4,016,258. The vasoactive intestinal peptide comprises a peptide containing a sequence of 28 amino acids in a single chain and having systemic vasodilator activity. It induces systemic hypotension and increases cardiac output on i.v. infusion. It increases hepatic arterial blood flow, increases blood sugar levels, and relaxes smooth muscle. It therefore appears to be of value in treatment of hypertension and peripheral vascular disease on parenteral administration, and as a bronchodilator on aerosol or parenteral administration.
Publications relating to the prior work regarding vasoactive intestinal peptides, are as follows:
1. S. I. Said and V. Mutt, Science 169, 1217 (1970) PA0 2. S. I. Said and V. Mutt, Nature (London) 225, 863 (1970) PA0 3. S. I. Said and V. Mutt, Eur. J. Biochem. 28, 199 (1972) PA0 4. M. Bodanszky, Y. S. Klausner, C. Yang Lin, V. Mutt and S. I. Said, J. Amer. Chem. Soc. 96, 4973 (1974) PA0 5. A. Nilsson, Febs Lett. 47, 284 (1974); Ibid. 60, 322 (1975) PA0 6. J. M. Polak, A. G. E. Pease, J. C. Garaud and S. R. Bloom, Gut 15, 720 (1974) PA0 7. S. I. Said and G. R. Faloona, New Engl. J. Med. 293, 155 (1975) PA0 8. S. I. Said and R. Rosenberg, Science 192, 907 (1976) PA0 9. K. Fuze, T. Hokfelt, S. I. Said and V. Mutt, Neuroscience Lett. 5, 241 (1977) PA0 10. M. G. Bryant, S. R. Bloom, J. M. Polak, R. H. Albuquerque, J. Modlin and A. G. E. Pease, Lancet 1, 991 (1976) PA0 11. A. Giachetti, S. I. Said, R. C. Reynolds, F. C. Koniges, Proc. Nat. Acad. Sci. U.S.A. 74, 3424 (1977) PA0 12. M. Bodanszky, C. Yang Lin, A. E. Yiotakis, V. Mutt and S. I. Said, Bioorg. Chem. 5, 339 (1976) PA0 (1) The free peptide, C-terminal amide, and L-pyroglutamyl derivative of VIP.sub.17-19 having the following amino acid sequence: EQU Met-Ala-Val PA0 (2) The free peptide C-terminal amide, and L-pyroglutamyl derivative of VIP.sub.16-19 having the following amino acid sequence: EQU Met-Ala-Val-Lys PA0 (3) The free peptide, and C-terminal amide of VIP.sub.16-20 having the following amino acid sequence: EQU Gln-Met-Ala-Val-Lys PA0 (4) The free peptide and C-terminal amide of VIP.sub.16-28 having the following amino acid sequence: EQU X-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Y-Leu-Z,
The present invention provides useful polypeptide fragments of the chicken peptide and methods for their preparation.